This Mentored Patient-Oriented Career Development Award (K23) application is to support Dr. David E. Fleck's developing expertise in the functional neuroimaging of bipolar disorder. During this award, the candidate will obtain training in imaging techniques, psychopathology, and research ethics. The candidate will integrate these newly-developed skills with existing experience in clinical research, neuropsychology, and statistics. At the conclusion of this award, the candidate will be uniquely positioned to function as an independent investigator capable of conducting high-quality neuroimaging research technically, theoretically, and as applied to clinical disorders. The candidate's long-term goal is to examine state-related neurocognitive changes to advance understanding of the neurophysiology and treatment of bipolar disorder. As a first step, the proposed research will examine the temporal (time-limited) brain dynamics of sustained attention in relation to mood state. The central hypothesis is that dorsolateral prefrontal cortex is "recruited" to maintain sustained attention in bipolar disorder due to subcortical brain abnormalities. Sustained attention decrements are predicted when distractibility is increased by mania, which interferes with limited channel capacity (executive) control processes of prefrontal cortex. To test this hypothesis, the candidate aims to examine differences in the temporal dynamics of prefrontal-striatal-thalamic brain circuit activation during a Continuous Performance Test (CPT) using high-field (4-tesla) functional magnetic resonance imaging (fMRI). Specifically, the candidate will examine chronometric changes during the simultaneous acquisition of fMRI and CPT data in three separate groups of manic bipolar, euthymic bipolar, and demographically similar healthy comparison subjects. If the central hypothesis is supported, it would suggest that manic distractibility has a mediating influence between the neurophysiological consequences of bipolar disorder and information processing efficiency. Clinically, positive results would indicate that neural reorganization allows patients with bipolar disorder to learn or enhance compensatory strategies in support of efficient information processing and better functional recovery. Although neuropsychological and anecdotal evidence suggest that this is indeed the case, corroborating neuroimaging data pertaining to the spatial and temporal dynamics of neural reorganization are not currently available.